Triphasic production of IFNγ by innate and adaptive lymphocytes following influenza A virus infection

Finney, G. E., Hargrave, K. E., Pingen, M. , Purnell, T., Todd, D., MacDonald, F., Worrell, J. C. and Macleod, M. K.L. (2023) Triphasic production of IFNγ by innate and adaptive lymphocytes following influenza A virus infection. Discovery Immunology, 2(1), kyad014. (doi: 10.1093/discim/kyad014) (PMID:37842651) (PMCID:PMC10568397)

Abstract

Interferon gamma (IFNγ) is a potent antiviral cytokine that can be produced by many innate and adaptive immune cells during infection. Currently, our understanding of which cells produce IFNγ and where they are located at different stages of an infection is limited. We have used reporter mice to investigate in vivo expression of Ifnγ mRNA in the lung and secondary lymphoid organs during and following influenza A virus (IAV) infection. We observed a triphasic production of Ifnγ expression. Unconventional T cells and innate lymphoid cells, particularly NK cells, were the dominant producers of early Ifnγ, while CD4 and CD8 T cells were the main producers by day 10 post-infection. Following viral clearance, some memory CD4 and CD8 T cells continued to express Ifnγ in the lungs and draining lymph node. Interestingly, Ifnγ production by lymph node Natural Killer (NK), NKT and innate lymphoid type 1 cells also continued to be above naïve levels, suggesting memory-like phenotypes for these cells. Analysis of the localisation of Ifnγ+ memory CD4 and CD8 T cells demonstrated that cytokine+ T cells were located near airways and in the lung parenchyma. Following a second IAV challenge, lung IAV specific CD8 T cells rapidly increased their expression of Ifnγ while CD4 T cells in the draining lymph node increased their Ifnγ response. Together, these data suggest that Ifnγ production fluctuates based on cellular source and location, both of which could impact subsequent immune responses.

• Item Type: Articles
• Additional Information: The work was funded by a University of Glasgow MVLS PhD studentship awarded to GEF and a Wellcome Trust Investigator Award (210703/Z/18/Z) to MKLM.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Todd, David and Worrell, Dr Julie and Finney, George and Pingen, Dr Marieke and Purnell, Mr Tom and Macleod, Dr Megan and Hargrave, Dr Kerrie
• Authors: Finney, G. E., Hargrave, K. E., Pingen, M., Purnell, T., Todd, D., MacDonald, F., Worrell, J. C., and Macleod, M. K.L.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Discovery Immunology
• Publisher: Oxford University Press
• ISSN: 2754-2483
• ISSN (Online): 2754-2483
• Published Online: 19 August 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Discovery Immunology 2(1): kyad014
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
302383		Communication between lung immune and stromal cells drives tissue protective immune memory	Megan MacLeod	Wellcome Trust (WELLCOTR)	210703/Z/18/Z	SII - Immunology & Infection